Therapeutic effects and the underlying mechanism of umbilical cord-derived mesenchymal stem cells for bleomycin induced lung injury in rats

Abstract

To study the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for bleomycin-induced pulmonary fibrosis in mice. UC-MSCs were isolated from the umbilical cord after parental consent. One hundred C57BL/6 mice were randomly divided into 4 groups (12 of these for preliminary experiment). Mice in the control group (n = 20) were instilled with PBS via trachea and NS was injected via the tail vein after 3 days. Mice in the stem cell group (n = 20) were instilled with PBS via trachea and were injected with MSC via the tail vein after 3 days. Mice in the bleomycin group (n = 24) were instilled with bleomycin via trachea and NS was injected via the tail vein after 3 days. Mice in the bleomycin plus stem cell group (n = 24) were instilled with bleomycin via trachea and were injected with MSCs via the tail vein after 3 days. All of the mice were sacrificed at the 21(th) day, and the lungs were immediately fixed with 4% paraformaldehyde for 48 h, embedded in paraffin and sectioned at 5 µmol/L thickness. The sections were stained with hematoxylin and eosin (H&E) and Masson-trichrome. Histopathological scoring of pulmonary fibrosis was performed according to Ashcroft's method. The concentrations of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-1were determined using immunohistochemistry. Compared with the bleomycin group, MSC transplantation significantly reduced pulmonary inflammation, fibrosis and deposition of collagen in the bleomycin plus stem cell group [(1.55 ± 0.51) vs (2.16 ± 0.77), and (1.45 ± 0.60) vs (2.32 ± 0.82), respectively, P < 0.05]. There was no difference between the control group and the stem cell group [(0.35 ± 0.49) vs (0.37 ± 0.50), P > 0.05]. The expression of MMP-2 in the bleomycin plus stem cell group was lower than the bleomycin group [(1.59 ± 0.59) vs (2.37 ± 0.68), P < 0.05], but there was no difference between the control group and the stem cell group [(0.80 ± 0.69) vs (0.84 ± 0.77), P > 0.05]. The expression of TIMP-1 in the bleomycin plus stem cell group was higher than the bleomycin group [(1.95 ± 0.58) vs (0.79 ± 0.71), P < 0.05], but there was no difference between the control group and the stem cell group [(1.10 ± 0.72) vs (1.32 ± 0.58), P > 0.05]. UC-MSC transplantation could relieve bleomycin-induced fibrosing alveolitis in mice. The mechanism might be related to the expression of MMP-2 and TIMP-1. UC-MSC had no effect on normal lungs.